Liver and intrahepatic bile ducts - tumor
Other malignancies
Cholangiocarcinoma (intrahepatic / peripheral)

Author: Deepali Jain, M.D. (see Authors page)

Revised: 6 June 2017, last major update February 2012

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PubMed Search: Cholangiocarcinoma [title] liver "intrahepatic bile duct"

Related topics: Intraductal cholangiocarcinoma, lymphoepithelioma-like cholangiocarcinoma

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Cite this page: Cholangiocarcinoma (intrahepatic / peripheral). PathologyOutlines.com website. http://pathologyoutlines.com/topic/livertumorcholangiocarcinoma.html. Accessed October 18th, 2017.
Definition / general
  • Adenocarcinoma arising from intrahepatic bile duct epithelial cells
  • Also called bile duct carcinoma
Clinical features
  • 10% of primary liver cancers
  • Diagnosis of exclusion - must rule out metastatic adenocarcinoma
  • High prevalence in southeast and eastern Asia, including Korea
  • 10 - 20% are associated with chronic bile stasis or cholangitis due to anabolic steroids, autosomal dominant polycystic disease, choledochal cysts, congenitally dilated hepatic ducts (Carolis disease), congenital hepatic fibrosis, intrahepatic lithiasis (5 - 10%), liver flukes Clonorchis sinensis or Opisthorchis viverrini, primary sclerosing cholangitis, Thorotrast
  • Rarely associated with neoplastic transformation of von Meyenburg complexes (Am J Surg Pathol 2000;24:1131)
  • Not associated with cirrhosis
  • Usually age 60+ years; no gender preference; but mean age 40 years in those with primary sclerosing cholangitis or chronic inflammatory bowel disease
  • 50 - 75% metastasize to regional lymph nodes, adrenals, brain, lungs, vertebrae or elsewhere at autopsy
  • 50% metastasize to perihilar, peripancreatic or paraaortic nodes
  • Death usually within 6 months; 5 year survival in resectable cases is 30%
  • Poor prognostic factors: lymphatic or intrahepatic metastases (Am J Surg Pathol 1999;23:892)
  • Klatskin tumor: hilar tumor arising at confluence of left and right hepatic ducts; clinically detected early due to obstruction
  • Laboratory: normal AFP, occasional hypercalcemia
Diagrams / tables

Images hosted on other servers:

Morphologic classification

Klatskin tumor

Classification
  • Liver Cancer Study Group of Japan: mass forming, periductal infiltrating, intraductal growth types (Radiographics 2009;29:683)
Case reports
  • 55 year old woman with synchronous, small cholangiocarcinoma and small hepatocellular carcinoma arising in two different dysplastic nodules, in an explant cirrhotic liver (Mod Pathol 2002;15:1096)
  • 61 year old woman with history of Carolis disease with extensive pulmonary vascular spread in the form of carcinomatous arteriopathy (Arch Pathol Lab Med 2002;126:717)
Gross description
  • Solitary, 7 - 10 cm, multinodular or diffuse small nodules < 1 cm
  • Grayish white and firm; often hepatomegaly and satellite nodules
  • No peripheral hyperemic zone seen in metastatic disease; rarely cirrhosis
  • Rarely bile stained, although may see bile in periphery; may invade portal vein
Gross images

Images hosted on other servers:

Various images

Mass forming cholangiocarcinomas


Periductal infiltrating cholangiocarcinoma

Klatskin tumor

Microscopic (histologic) description
  • Moderate to well differentiated adenocarcinoma with glandular and tubular structures, mucin production and dense desmoplasia
  • Epithelial cells are anaplastic, cuboidal to columnar with eosinophilic cytoplasm and round central nuclei, tumor cells are heterogeneous even within the same gland but resemble bile duct cells, not hepatocytes
  • Tumor spreads along hepatic plates, duct walls, via nerves (perineural invasion in 81%) but not sinusoidal
  • Stroma may be circumferential around glands; associated with neutrophils
  • Variable vascular invasion; no bile production
  • Patterns: adenosquamous, clear cell, colloid, lymphoepithelioma-like, mucoepidermoid, osteoclast giant cell, rhabdoid, sarcomatous, signet ring
  • Bile ductular carcinoma: composed of small glands resembling reactive bile ductules, NCAM+ (Histopathology 2007;51:390)
  • Cholangiolocellular carcinoma: cholangiocarcinoma, hepatocellular carcinoma and background cirrhosis; must differentiate from hepatocellular carcinoma with CK19+, CK7+ (Histopathology 2006;49:138)
Microscopic (histologic) images

Images hosted on other servers:

Various images

Cholangiocarcinoma


Mass forming cholangiocarcinomas


Associated with multiple von Meyenburg complexes

Comparison: hepatocellular carcinoma versus cholangiocarcinoma (left to right): H&E, MOC31, pCEA

Various images

Cytology description
  • Abundant, finely granular cytoplasm
Positive stains
Negative stains
Molecular / cytogenetics description
  • Kras mutations
  • Downregulation of β-catenin, aberrant expression and activation of ErbB, HGF, IL6
Differential diagnosis